UA124616C2 - Зв'язуюче тау-білок антитіло - Google Patents

Info

Publication number

UA124616C2

UA124616C2 UAA201711739A UAA201711739A UA124616C2 UA 124616 C2 UA124616 C2 UA 124616C2 UA A201711739 A UAA201711739 A UA A201711739A UA A201711739 A UAA201711739 A UA A201711739A UA 124616 C2 UA124616 C2 UA 124616C2

Authority

UA

Ukraine

Prior art keywords

tau

antibody

binding

rgo

binding fragment

Prior art date

2015-07-06

Links

• Espacenet
• Global Dossier
• Discuss

• 230000027455 binding Effects 0.000 title claims abstract description 716
• 102000013498 tau Proteins Human genes 0.000 title claims abstract description 465
• 108010026424 tau Proteins Proteins 0.000 title claims abstract description 465
• 238000000034 method Methods 0.000 claims abstract description 45
• 150000007523 nucleic acids Chemical class 0.000 claims abstract description 41
• 108020004707 nucleic acids Proteins 0.000 claims abstract description 31
• 102000039446 nucleic acids Human genes 0.000 claims abstract description 31
• 238000011282 treatment Methods 0.000 claims abstract description 24
• 239000013604 expression vector Substances 0.000 claims abstract description 18
• 238000010367 cloning Methods 0.000 claims abstract description 10
• 238000003745 diagnosis Methods 0.000 claims abstract description 7
• 239000013599 cloning vector Substances 0.000 claims abstract description 3
• 239000012634 fragment Substances 0.000 claims description 369
• 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 claims description 55
• 102000057063 human MAPT Human genes 0.000 claims description 55
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 27
• 125000000539 amino acid group Chemical group 0.000 claims description 26
• 208000024827 Alzheimer disease Diseases 0.000 claims description 24
• 239000000203 mixture Substances 0.000 claims description 23
• 208000034799 Tauopathies Diseases 0.000 claims description 21
• 235000010469 Glycine max Nutrition 0.000 claims description 19
• 108020004414 DNA Proteins 0.000 claims description 18
• 244000068988 Glycine max Species 0.000 claims description 13
• 210000004556 brain Anatomy 0.000 claims description 11
• 230000008859 change Effects 0.000 claims description 6
• 101150060303 SOK2 gene Proteins 0.000 claims description 5
• 238000002955 isolation Methods 0.000 claims description 5
• 239000013589 supplement Substances 0.000 claims description 3
• 238000012360 testing method Methods 0.000 claims description 3
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical group CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 2
• 239000000284 extract Substances 0.000 claims description 2
• 244000005894 Albizia lebbeck Species 0.000 claims 7
• 241001655798 Taku Species 0.000 claims 6
• 241001026509 Kata Species 0.000 claims 5
• 235000013312 flour Nutrition 0.000 claims 5
• WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 claims 4
• YPMOAQISONSSNL-UHFFFAOYSA-N 8-hydroxyoctyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCCCCCO YPMOAQISONSSNL-UHFFFAOYSA-N 0.000 claims 3
• OWNRRUFOJXFKCU-UHFFFAOYSA-N Bromadiolone Chemical compound C=1C=C(C=2C=CC(Br)=CC=2)C=CC=1C(O)CC(C=1C(OC2=CC=CC=C2C=1O)=O)C1=CC=CC=C1 OWNRRUFOJXFKCU-UHFFFAOYSA-N 0.000 claims 3
• ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 claims 3
• 101000636705 Homo sapiens NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial Proteins 0.000 claims 3
• 201000002531 Karyomegalic interstitial nephritis Diseases 0.000 claims 3
• 102100031919 NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial Human genes 0.000 claims 3
• 241000283965 Ochotona princeps Species 0.000 claims 3
• 235000016787 Piper methysticum Nutrition 0.000 claims 3
• 240000005546 Piper methysticum Species 0.000 claims 3
• 244000240602 cacao Species 0.000 claims 3
• 241001116389 Aloe Species 0.000 claims 2
• 244000099147 Ananas comosus Species 0.000 claims 2
• 235000007119 Ananas comosus Nutrition 0.000 claims 2
• 235000003913 Coccoloba uvifera Nutrition 0.000 claims 2
• 101100369915 Drosophila melanogaster stas gene Proteins 0.000 claims 2
• 101000654674 Homo sapiens Semaphorin-6A Proteins 0.000 claims 2
• 101000850431 Homo sapiens Synaptic vesicle membrane protein VAT-1 homolog Proteins 0.000 claims 2
• 241001397173 Kali <angiosperm> Species 0.000 claims 2
• 241000468053 Obodhiang virus Species 0.000 claims 2
• 240000008976 Pterocarpus marsupium Species 0.000 claims 2
• 102100032795 Semaphorin-6A Human genes 0.000 claims 2
• 102100033475 Synaptic vesicle membrane protein VAT-1 homolog Human genes 0.000 claims 2
• 241001080137 Tosta Species 0.000 claims 2
• 241000289690 Xenarthra Species 0.000 claims 2
• FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims 2
• 235000011399 aloe vera Nutrition 0.000 claims 2
• LVKZSFMYNWRPJX-UHFFFAOYSA-N benzenearsonic acid Natural products O[As](O)(=O)C1=CC=CC=C1 LVKZSFMYNWRPJX-UHFFFAOYSA-N 0.000 claims 2
• 229920006012 semi-aromatic polyamide Polymers 0.000 claims 2
• WLNBMPZUVDTASE-HXIISURNSA-N (2r,3r,4s,5r)-2-amino-3,4,5,6-tetrahydroxyhexanal;sulfuric acid Chemical compound [O-]S([O-])(=O)=O.O=C[C@H]([NH3+])[C@@H](O)[C@H](O)[C@H](O)CO.O=C[C@H]([NH3+])[C@@H](O)[C@H](O)[C@H](O)CO WLNBMPZUVDTASE-HXIISURNSA-N 0.000 claims 1
• RGHMISIYKIHAJW-UHFFFAOYSA-N 3,4-dihydroxymandelic acid Chemical compound OC(=O)C(O)C1=CC=C(O)C(O)=C1 RGHMISIYKIHAJW-UHFFFAOYSA-N 0.000 claims 1
• GRNHLFULJDXJKR-UHFFFAOYSA-N 3-(2-sulfanylethyl)-1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)N(CCS)C(=O)NC2=C1 GRNHLFULJDXJKR-UHFFFAOYSA-N 0.000 claims 1
• 108091008717 AR-A Proteins 0.000 claims 1
• 241001436679 Adama Species 0.000 claims 1
• ORILYTVJVMAKLC-UHFFFAOYSA-N Adamantane Natural products C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims 1
• 101001015038 Albizia kalkora Kunitz-type trypsin inhibitor alpha chain Proteins 0.000 claims 1
• 101500021165 Aplysia californica Myomodulin-A Proteins 0.000 claims 1
• 244000075850 Avena orientalis Species 0.000 claims 1
• 235000007319 Avena orientalis Nutrition 0.000 claims 1
• 241000282461 Canis lupus Species 0.000 claims 1
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims 1
• 102100027835 Cell death regulator Aven Human genes 0.000 claims 1
• 241000283153 Cetacea Species 0.000 claims 1
• 101100102516 Clonostachys rogersoniana vern gene Proteins 0.000 claims 1
• 241001327708 Coriaria sarmentosa Species 0.000 claims 1
• 229920000742 Cotton Polymers 0.000 claims 1
• 235000017274 Diospyros sandwicensis Nutrition 0.000 claims 1
• 102100037815 Fas apoptotic inhibitory molecule 3 Human genes 0.000 claims 1
• 102100040870 Glycine amidinotransferase, mitochondrial Human genes 0.000 claims 1
• 206010018910 Haemolysis Diseases 0.000 claims 1
• 101000698131 Homo sapiens Cell death regulator Aven Proteins 0.000 claims 1
• 101000878510 Homo sapiens Fas apoptotic inhibitory molecule 3 Proteins 0.000 claims 1
• 101000893303 Homo sapiens Glycine amidinotransferase, mitochondrial Proteins 0.000 claims 1
• 101000633680 Homo sapiens Tetratricopeptide repeat protein 37 Proteins 0.000 claims 1
• 241000947136 Jarava media Species 0.000 claims 1
• 241000120527 Kemerovo virus Species 0.000 claims 1
• 241000282838 Lama Species 0.000 claims 1
• 229940110339 Long-acting muscarinic antagonist Drugs 0.000 claims 1
• 241001446467 Mama Species 0.000 claims 1
• 241001291562 Martes pennanti Species 0.000 claims 1
• 241000751119 Mila <angiosperm> Species 0.000 claims 1
• 101100498160 Mus musculus Dach1 gene Proteins 0.000 claims 1
• XQVWYOYUZDUNRW-UHFFFAOYSA-N N-Phenyl-1-naphthylamine Chemical compound C=1C=CC2=CC=CC=C2C=1NC1=CC=CC=C1 XQVWYOYUZDUNRW-UHFFFAOYSA-N 0.000 claims 1
• ROJGIRXXBBBMPL-UHFFFAOYSA-N N-hydroxy-2-propylpentanamide Chemical compound CCCC(CCC)C(=O)NO ROJGIRXXBBBMPL-UHFFFAOYSA-N 0.000 claims 1
• 102100026747 Osteomodulin Human genes 0.000 claims 1
• 101710114565 Osteomodulin Proteins 0.000 claims 1
• 241000697033 Ostracion meleagris Species 0.000 claims 1
• 241001256807 Pasma Species 0.000 claims 1
• 241001482237 Pica Species 0.000 claims 1
• 241001310793 Podium Species 0.000 claims 1
• 235000011449 Rosa Nutrition 0.000 claims 1
• 108091006583 SLC14A2 Proteins 0.000 claims 1
• 244000272264 Saussurea lappa Species 0.000 claims 1
• 235000006784 Saussurea lappa Nutrition 0.000 claims 1
• 241000270295 Serpentes Species 0.000 claims 1
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 1
• 241000120020 Tela Species 0.000 claims 1
• 102100029210 Tetratricopeptide repeat protein 37 Human genes 0.000 claims 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims 1
• 244000111306 Torreya nucifera Species 0.000 claims 1
• 235000006732 Torreya nucifera Nutrition 0.000 claims 1
• 241000209140 Triticum Species 0.000 claims 1
• 235000021307 Triticum Nutrition 0.000 claims 1
• CCAZWUJBLXKBAY-ULZPOIKGSA-N Tutin Chemical compound C([C@]12[C@@H]3O[C@@H]3[C@@]3(O)[C@H]4C(=O)O[C@@H]([C@H]([C@]32C)O)[C@H]4C(=C)C)O1 CCAZWUJBLXKBAY-ULZPOIKGSA-N 0.000 claims 1
• 229910000842 Zamak Inorganic materials 0.000 claims 1
• 208000020329 Zika virus infectious disease Diseases 0.000 claims 1
• 206010000496 acne Diseases 0.000 claims 1
• 239000011717 all-trans-retinol Substances 0.000 claims 1
• 235000019169 all-trans-retinol Nutrition 0.000 claims 1
• 210000000436 anus Anatomy 0.000 claims 1
• 208000006673 asthma Diseases 0.000 claims 1
• 235000014510 cooky Nutrition 0.000 claims 1
• 235000005583 doda Nutrition 0.000 claims 1
• 244000144992 flock Species 0.000 claims 1
• 235000011389 fruit/vegetable juice Nutrition 0.000 claims 1
• 239000011521 glass Substances 0.000 claims 1
• 230000008588 hemolysis Effects 0.000 claims 1
• 235000000010 nanu Nutrition 0.000 claims 1
• 244000082862 nanu Species 0.000 claims 1
• 239000002574 poison Substances 0.000 claims 1
• 231100000614 poison Toxicity 0.000 claims 1
• 238000000682 scanning probe acoustic microscopy Methods 0.000 claims 1
• 238000000926 separation method Methods 0.000 claims 1
• 239000010902 straw Substances 0.000 claims 1
• LZNWYQJJBLGYLT-UHFFFAOYSA-N tenoxicam Chemical compound OC=1C=2SC=CC=2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 LZNWYQJJBLGYLT-UHFFFAOYSA-N 0.000 claims 1
• UQFSVBXCNGCBBW-UHFFFAOYSA-M tetraethylammonium iodide Chemical compound [I-].CC[N+](CC)(CC)CC UQFSVBXCNGCBBW-UHFFFAOYSA-M 0.000 claims 1
• 229940035289 tobi Drugs 0.000 claims 1
• NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 claims 1
• 230000001256 tonic effect Effects 0.000 claims 1
• VLCQZHSMCYCDJL-UHFFFAOYSA-N tribenuron methyl Chemical compound COC(=O)C1=CC=CC=C1S(=O)(=O)NC(=O)N(C)C1=NC(C)=NC(OC)=N1 VLCQZHSMCYCDJL-UHFFFAOYSA-N 0.000 claims 1
• 208000007004 trichohepatoenteric syndrome Diseases 0.000 claims 1
• 229910052724 xenon Inorganic materials 0.000 claims 1
• FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 claims 1
• 210000004027 cell Anatomy 0.000 description 84
• 108090000623 proteins and genes Proteins 0.000 description 52
• 235000001014 amino acid Nutrition 0.000 description 44
• 229940024606 amino acid Drugs 0.000 description 42
• 150000001413 amino acids Chemical class 0.000 description 42
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 37
• 108090000765 processed proteins & peptides Proteins 0.000 description 37
• 108010029485 Protein Isoforms Proteins 0.000 description 34
• 102000001708 Protein Isoforms Human genes 0.000 description 34
• 239000012636 effector Substances 0.000 description 33
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 32
• 239000013598 vector Substances 0.000 description 32
• 102000004169 proteins and genes Human genes 0.000 description 31
• 125000003275 alpha amino acid group Chemical group 0.000 description 30
• 201000010099 disease Diseases 0.000 description 30
• 235000018102 proteins Nutrition 0.000 description 28
• 102000004196 processed proteins & peptides Human genes 0.000 description 26
• 238000002474 experimental method Methods 0.000 description 21
• 230000014509 gene expression Effects 0.000 description 21
• 241000700159 Rattus Species 0.000 description 19
• -1 amino, imino Chemical group 0.000 description 19
• 229920000642 polymer Polymers 0.000 description 18
• 238000004458 analytical method Methods 0.000 description 17
• 239000000872 buffer Substances 0.000 description 17
• 229920001184 polypeptide Polymers 0.000 description 17
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 16
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 16
• 210000003719 b-lymphocyte Anatomy 0.000 description 16
• 239000000427 antigen Substances 0.000 description 15
• 108091007433 antigens Proteins 0.000 description 15
• 102000036639 antigens Human genes 0.000 description 15
• 230000035772 mutation Effects 0.000 description 15
• 239000000126 substance Substances 0.000 description 14
• 230000002776 aggregation Effects 0.000 description 13
• 238000004220 aggregation Methods 0.000 description 13
• 238000005516 engineering process Methods 0.000 description 13
• 239000003814 drug Substances 0.000 description 12
• 230000000694 effects Effects 0.000 description 12
• 230000009261 transgenic effect Effects 0.000 description 12
• 206010012289 Dementia Diseases 0.000 description 11
• 229920001223 polyethylene glycol Polymers 0.000 description 11
• 238000012216 screening Methods 0.000 description 11
• 239000000243 solution Substances 0.000 description 11
• 230000001225 therapeutic effect Effects 0.000 description 11
• 241000699670 Mus sp. Species 0.000 description 10
• 108010025020 Nerve Growth Factor Proteins 0.000 description 10
• 108091028043 Nucleic acid sequence Proteins 0.000 description 10
• 239000012472 biological sample Substances 0.000 description 10
• 210000004602 germ cell Anatomy 0.000 description 10
• 230000003472 neutralizing effect Effects 0.000 description 10
• 230000007170 pathology Effects 0.000 description 10
• 238000006467 substitution reaction Methods 0.000 description 10
• 239000006228 supernatant Substances 0.000 description 10
• 210000001519 tissue Anatomy 0.000 description 10
• 241000699666 Mus <mouse, genus> Species 0.000 description 9
• 241000897276 Termes Species 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 239000000523 sample Substances 0.000 description 9
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• 241001465754 Metazoa Species 0.000 description 8
• 238000005481 NMR spectroscopy Methods 0.000 description 8
• 238000003556 assay Methods 0.000 description 8
• 230000003053 immunization Effects 0.000 description 8
• 230000001575 pathological effect Effects 0.000 description 8
• 230000002285 radioactive effect Effects 0.000 description 8
• 229940124597 therapeutic agent Drugs 0.000 description 8
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
• 108060003951 Immunoglobulin Proteins 0.000 description 7
• 239000013543 active substance Substances 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 150000001875 compounds Chemical class 0.000 description 7
• 238000002649 immunization Methods 0.000 description 7
• 102000018358 immunoglobulin Human genes 0.000 description 7
• 238000004519 manufacturing process Methods 0.000 description 7
• 238000003752 polymerase chain reaction Methods 0.000 description 7
• 238000001262 western blot Methods 0.000 description 7
• 101000854943 Enterobacteria phage T4 Valyl-tRNA ligase modifier Proteins 0.000 description 6
• 201000011240 Frontotemporal dementia Diseases 0.000 description 6
• 102000015336 Nerve Growth Factor Human genes 0.000 description 6
• 208000027089 Parkinsonian disease Diseases 0.000 description 6
• 206010034010 Parkinsonism Diseases 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 238000004113 cell culture Methods 0.000 description 6
• 238000003776 cleavage reaction Methods 0.000 description 6
• 238000001514 detection method Methods 0.000 description 6
• 238000002347 injection Methods 0.000 description 6
• 239000007924 injection Substances 0.000 description 6
• 239000012528 membrane Substances 0.000 description 6
• 229940053128 nerve growth factor Drugs 0.000 description 6
• 230000007017 scission Effects 0.000 description 6
• 238000011830 transgenic mouse model Methods 0.000 description 6
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
• 108091026890 Coding region Proteins 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 241000699660 Mus musculus Species 0.000 description 5
• 101100269376 Mus musculus Agfg2 gene Proteins 0.000 description 5
• 108091005804 Peptidases Proteins 0.000 description 5
• 108020004511 Recombinant DNA Proteins 0.000 description 5
• 238000001042 affinity chromatography Methods 0.000 description 5
• 230000008499 blood brain barrier function Effects 0.000 description 5
• 210000001218 blood-brain barrier Anatomy 0.000 description 5
• 229940088598 enzyme Drugs 0.000 description 5
• 238000012744 immunostaining Methods 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 238000005259 measurement Methods 0.000 description 5
• 239000002609 medium Substances 0.000 description 5
• JLESVLCTIOAHPT-UHFFFAOYSA-N mmai Chemical compound C1=C(C)C(OC)=CC2=C1CC(N)C2 JLESVLCTIOAHPT-UHFFFAOYSA-N 0.000 description 5
• 230000004048 modification Effects 0.000 description 5
• 238000012986 modification Methods 0.000 description 5
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 5
• 238000002360 preparation method Methods 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 238000001228 spectrum Methods 0.000 description 5
• 108010088751 Albumins Proteins 0.000 description 4
• 102000009027 Albumins Human genes 0.000 description 4
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 4
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 4
• 239000004475 Arginine Substances 0.000 description 4
• 241000283707 Capra Species 0.000 description 4
• 239000004471 Glycine Substances 0.000 description 4
• 108700005091 Immunoglobulin Genes Proteins 0.000 description 4
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
• 239000004472 Lysine Substances 0.000 description 4
• 102000029749 Microtubule Human genes 0.000 description 4
• 108091022875 Microtubule Proteins 0.000 description 4
• 102000007072 Nerve Growth Factors Human genes 0.000 description 4
• DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 4
• 238000007792 addition Methods 0.000 description 4
• 150000001408 amides Chemical group 0.000 description 4
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 4
• 238000013459 approach Methods 0.000 description 4
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
• 229960002685 biotin Drugs 0.000 description 4
• 235000020958 biotin Nutrition 0.000 description 4
• 239000011616 biotin Substances 0.000 description 4
• 210000003169 central nervous system Anatomy 0.000 description 4
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
• 230000021615 conjugation Effects 0.000 description 4
• 239000013078 crystal Substances 0.000 description 4
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
• 230000003993 interaction Effects 0.000 description 4
• 210000004962 mammalian cell Anatomy 0.000 description 4
• 238000013507 mapping Methods 0.000 description 4
• 210000004688 microtubule Anatomy 0.000 description 4
• 239000013642 negative control Substances 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• 239000008194 pharmaceutical composition Substances 0.000 description 4
• 230000001105 regulatory effect Effects 0.000 description 4
• 230000003595 spectral effect Effects 0.000 description 4
• 150000003573 thiols Chemical class 0.000 description 4
• 238000012546 transfer Methods 0.000 description 4
• 238000002424 x-ray crystallography Methods 0.000 description 4
• PFFIDZXUXFLSSR-UHFFFAOYSA-N 1-methyl-N-[2-(4-methylpentan-2-yl)-3-thienyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound S1C=CC(NC(=O)C=2C(=NN(C)C=2)C(F)(F)F)=C1C(C)CC(C)C PFFIDZXUXFLSSR-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical group CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
• 101100460719 Mus musculus Noto gene Proteins 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 239000004365 Protease Substances 0.000 description 3
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 3
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical group CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
• 101100187345 Xenopus laevis noto gene Proteins 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 239000003963 antioxidant agent Substances 0.000 description 3
• 230000008335 axon cargo transport Effects 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• 230000004071 biological effect Effects 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 229940098773 bovine serum albumin Drugs 0.000 description 3
• 210000004899 c-terminal region Anatomy 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 230000001413 cellular effect Effects 0.000 description 3
• 230000001268 conjugating effect Effects 0.000 description 3
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
• 235000018417 cysteine Nutrition 0.000 description 3
• 238000012217 deletion Methods 0.000 description 3
• 230000037430 deletion Effects 0.000 description 3
• 239000008121 dextrose Substances 0.000 description 3
• 238000010790 dilution Methods 0.000 description 3
• 239000012895 dilution Substances 0.000 description 3
• 230000002518 glial effect Effects 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• 229940072221 immunoglobulins Drugs 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 3
• 239000003550 marker Substances 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• 229910021645 metal ion Inorganic materials 0.000 description 3
• 150000002739 metals Chemical class 0.000 description 3
• 229930182817 methionine Natural products 0.000 description 3
• 238000012544 monitoring process Methods 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 239000003900 neurotrophic factor Substances 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• 108091033319 polynucleotide Proteins 0.000 description 3
• 102000040430 polynucleotide Human genes 0.000 description 3
• 239000002157 polynucleotide Substances 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 238000012545 processing Methods 0.000 description 3
• 230000000750 progressive effect Effects 0.000 description 3
• 230000004845 protein aggregation Effects 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 239000013049 sediment Substances 0.000 description 3
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 229920001059 synthetic polymer Polymers 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• URYYVOIYTNXXBN-OWOJBTEDSA-N trans-cyclooctene Chemical compound C1CCC\C=C\CC1 URYYVOIYTNXXBN-OWOJBTEDSA-N 0.000 description 3
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
• 239000004474 valine Chemical group 0.000 description 3
• 238000012800 visualization Methods 0.000 description 3
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
• PVVTWNMXEHROIA-UHFFFAOYSA-N 2-(3-hydroxypropyl)-1h-quinazolin-4-one Chemical compound C1=CC=C2NC(CCCO)=NC(=O)C2=C1 PVVTWNMXEHROIA-UHFFFAOYSA-N 0.000 description 2
• JVJUWEFOGFCHKR-UHFFFAOYSA-N 2-(diethylamino)ethyl 1-(3,4-dimethylphenyl)cyclopentane-1-carboxylate;hydrochloride Chemical class Cl.C=1C=C(C)C(C)=CC=1C1(C(=O)OCCN(CC)CC)CCCC1 JVJUWEFOGFCHKR-UHFFFAOYSA-N 0.000 description 2
• XEYLAWVXYZUVDD-UHFFFAOYSA-N 2-hydroxy-5-(2-methylprop-2-enoylamino)benzoic acid Chemical compound CC(=C)C(=O)NC1=CC=C(O)C(C(O)=O)=C1 XEYLAWVXYZUVDD-UHFFFAOYSA-N 0.000 description 2
• 102000007469 Actins Human genes 0.000 description 2
• 108010085238 Actins Proteins 0.000 description 2
• 208000037259 Amyloid Plaque Diseases 0.000 description 2
• 102000008102 Ankyrins Human genes 0.000 description 2
• 108010049777 Ankyrins Proteins 0.000 description 2
• CJLHTKGWEUGORV-UHFFFAOYSA-N Artemin Chemical compound C1CC2(C)C(O)CCC(=C)C2(O)C2C1C(C)C(=O)O2 CJLHTKGWEUGORV-UHFFFAOYSA-N 0.000 description 2
• 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 2
• 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 2
• 102100037597 Brain-derived neurotrophic factor Human genes 0.000 description 2
• 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
• 102000003930 C-Type Lectins Human genes 0.000 description 2
• 108090000342 C-Type Lectins Proteins 0.000 description 2
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 2
• 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 description 2
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
• 208000011990 Corticobasal Degeneration Diseases 0.000 description 2
• 229920002307 Dextran Polymers 0.000 description 2
• 208000009093 Diffuse Neurofibrillary Tangles with Calcification Diseases 0.000 description 2
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
• 201000010374 Down Syndrome Diseases 0.000 description 2
• 238000004435 EPR spectroscopy Methods 0.000 description 2
• 102400001368 Epidermal growth factor Human genes 0.000 description 2
• 101800003838 Epidermal growth factor Proteins 0.000 description 2
• 102000003951 Erythropoietin Human genes 0.000 description 2
• 108090000394 Erythropoietin Proteins 0.000 description 2
• 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
• 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
• 102000016359 Fibronectins Human genes 0.000 description 2
• 108010067306 Fibronectins Proteins 0.000 description 2
• 206010018341 Gliosis Diseases 0.000 description 2
• 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
• 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
• 102100021866 Hepatocyte growth factor Human genes 0.000 description 2
• 241000238631 Hexapoda Species 0.000 description 2
• 101000654734 Homo sapiens Septin-4 Proteins 0.000 description 2
• 102000000589 Interleukin-1 Human genes 0.000 description 2
• 108010002352 Interleukin-1 Proteins 0.000 description 2
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
• 102000004058 Leukemia inhibitory factor Human genes 0.000 description 2
• 108090000581 Leukemia inhibitory factor Proteins 0.000 description 2
• 102000019298 Lipocalin Human genes 0.000 description 2
• 108050006654 Lipocalin Proteins 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 208000036626 Mental retardation Diseases 0.000 description 2
• 208000026072 Motor neurone disease Diseases 0.000 description 2
• 206010068871 Myotonic dystrophy Diseases 0.000 description 2
• 102000010803 Netrins Human genes 0.000 description 2
• 108010063605 Netrins Proteins 0.000 description 2
• 108090000099 Neurotrophin-4 Proteins 0.000 description 2
• 208000014060 Niemann-Pick disease Diseases 0.000 description 2
• 208000037658 Parkinson-dementia complex of Guam Diseases 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 208000000609 Pick Disease of the Brain Diseases 0.000 description 2
• 206010035226 Plasma cell myeloma Diseases 0.000 description 2
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
• 208000036757 Postencephalitic parkinsonism Diseases 0.000 description 2
• 102000029797 Prion Human genes 0.000 description 2
• 108091000054 Prion Proteins 0.000 description 2
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
• 229910019567 Re Re Inorganic materials 0.000 description 2
• 206010070834 Sensitisation Diseases 0.000 description 2
• 102100032743 Septin-4 Human genes 0.000 description 2
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
• 108010090804 Streptavidin Proteins 0.000 description 2
• 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 2
• 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• 239000004473 Threonine Substances 0.000 description 2
• 102000004357 Transferases Human genes 0.000 description 2
• 108090000992 Transferases Proteins 0.000 description 2
• 102000004338 Transferrin Human genes 0.000 description 2
• 108090000901 Transferrin Proteins 0.000 description 2
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
• 238000002441 X-ray diffraction Methods 0.000 description 2
• 238000002835 absorbance Methods 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 230000009824 affinity maturation Effects 0.000 description 2
• 235000004279 alanine Nutrition 0.000 description 2
• 208000013968 amyotrophic lateral sclerosis-parkinsonism-dementia complex Diseases 0.000 description 2
• 208000014450 amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 Diseases 0.000 description 2
• 239000012491 analyte Substances 0.000 description 2
• 239000004599 antimicrobial Substances 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 229940009098 aspartate Drugs 0.000 description 2
• 230000006399 behavior Effects 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 229940112869 bone morphogenetic protein Drugs 0.000 description 2
• 210000000133 brain stem Anatomy 0.000 description 2
• 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 2
• 239000004067 bulking agent Substances 0.000 description 2
• 239000001110 calcium chloride Substances 0.000 description 2
• 229910001628 calcium chloride Inorganic materials 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 239000005018 casein Substances 0.000 description 2
• BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 2
• 235000021240 caseins Nutrition 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
• 239000002738 chelating agent Substances 0.000 description 2
• 238000006243 chemical reaction Methods 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 238000005352 clarification Methods 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 239000012228 culture supernatant Substances 0.000 description 2
• 238000012258 culturing Methods 0.000 description 2
• 230000006240 deamidation Effects 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 208000017004 dementia pugilistica Diseases 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 208000035475 disorder Diseases 0.000 description 2
• 238000010494 dissociation reaction Methods 0.000 description 2
• 230000005593 dissociations Effects 0.000 description 2
• ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 238000001378 electrochemiluminescence detection Methods 0.000 description 2
• 210000002257 embryonic structure Anatomy 0.000 description 2
• 229940116977 epidermal growth factor Drugs 0.000 description 2
• 229940105423 erythropoietin Drugs 0.000 description 2
• 210000003527 eukaryotic cell Anatomy 0.000 description 2
• 230000004424 eye movement Effects 0.000 description 2
• 239000012894 fetal calf serum Substances 0.000 description 2
• 229940126864 fibroblast growth factor Drugs 0.000 description 2
• ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
• 102000013069 gamma-Crystallins Human genes 0.000 description 2
• 108010079934 gamma-Crystallins Proteins 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 230000007387 gliosis Effects 0.000 description 2
• 229930195712 glutamate Natural products 0.000 description 2
• 235000013922 glutamic acid Nutrition 0.000 description 2
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
• 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
• 210000001320 hippocampus Anatomy 0.000 description 2
• 210000004408 hybridoma Anatomy 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 210000000987 immune system Anatomy 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 229910052742 iron Inorganic materials 0.000 description 2
• 229960000310 isoleucine Drugs 0.000 description 2
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 238000011068 loading method Methods 0.000 description 2
• 229920001427 mPEG Polymers 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 238000001823 molecular biology technique Methods 0.000 description 2
• 239000000178 monomer Substances 0.000 description 2
• 208000005264 motor neuron disease Diseases 0.000 description 2
• 201000000050 myeloid neoplasm Diseases 0.000 description 2
• 239000002105 nanoparticle Substances 0.000 description 2
• 230000000926 neurological effect Effects 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• 239000000816 peptidomimetic Substances 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
• 230000008488 polyadenylation Effects 0.000 description 2
• 229920001281 polyalkylene Polymers 0.000 description 2
• 229940057838 polyethylene glycol 4000 Drugs 0.000 description 2
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• 208000000170 postencephalitic Parkinson disease Diseases 0.000 description 2
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 2
• 230000008707 rearrangement Effects 0.000 description 2
• 229940044551 receptor antagonist Drugs 0.000 description 2
• 239000002464 receptor antagonist Substances 0.000 description 2
• 230000008929 regeneration Effects 0.000 description 2
• 238000011069 regeneration method Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 238000010839 reverse transcription Methods 0.000 description 2
• 210000003705 ribosome Anatomy 0.000 description 2
• 238000005070 sampling Methods 0.000 description 2
• 230000008313 sensitization Effects 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 238000002603 single-photon emission computed tomography Methods 0.000 description 2
• 238000002741 site-directed mutagenesis Methods 0.000 description 2
• 239000002904 solvent Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 230000006641 stabilisation Effects 0.000 description 2
• 238000011105 stabilization Methods 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 210000000130 stem cell Anatomy 0.000 description 2
• 230000002739 subcortical effect Effects 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• 239000003053 toxin Substances 0.000 description 2
• 231100000765 toxin Toxicity 0.000 description 2
• 108700012359 toxins Proteins 0.000 description 2
• 230000005030 transcription termination Effects 0.000 description 2
• 239000012581 transferrin Substances 0.000 description 2
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 2
• 210000004885 white matter Anatomy 0.000 description 2
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
• VHNYOQKVZQVBLC-RTCGXNAVSA-N (4r,7e,9as)-7-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-4-(3,4,5-trifluorophenyl)-1,3,4,8,9,9a-hexahydropyrido[2,1-c][1,4]oxazin-6-one Chemical compound C1([C@@H]2COC[C@@H]3CC\C(C(N32)=O)=C/C=2C=C(C(=CC=2)N2C=C(C)N=C2)OC)=CC(F)=C(F)C(F)=C1 VHNYOQKVZQVBLC-RTCGXNAVSA-N 0.000 description 1
• JEQYWIBQETUPEM-UHFFFAOYSA-N (ethenyldisulfanyl)ethene Chemical compound C=CSSC=C JEQYWIBQETUPEM-UHFFFAOYSA-N 0.000 description 1
• AYNDKKQQUZPETC-NXVVXOECSA-N (z)-2,3-bis(2,4,5-trimethylthiophen-3-yl)but-2-enedinitrile Chemical compound CC1=C(C)SC(C)=C1\C(C#N)=C(\C#N)C1=C(C)SC(C)=C1C AYNDKKQQUZPETC-NXVVXOECSA-N 0.000 description 1
• 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
• OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-UHFFFAOYSA-N 0.000 description 1
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
• UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
• 125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 description 1
• PMJHNEFCWLUZBC-UHFFFAOYSA-N 4-(4-amino-3-methylphenyl)-2,6,6-trimethylcyclohexa-1,3-dien-1-amine Chemical compound CC1=C(N)C(C)(C)CC(C=2C=C(C)C(N)=CC=2)=C1 PMJHNEFCWLUZBC-UHFFFAOYSA-N 0.000 description 1
• ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
• CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
• 108010066676 Abrin Proteins 0.000 description 1
• 108010000239 Aequorin Proteins 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 229920000856 Amylose Polymers 0.000 description 1
• 102400000068 Angiostatin Human genes 0.000 description 1
• 108010079709 Angiostatins Proteins 0.000 description 1
• 206010002942 Apathy Diseases 0.000 description 1
• 241001521218 Aphthovirus Asia Species 0.000 description 1
• 102100026376 Artemin Human genes 0.000 description 1
• 101710205806 Artemin Proteins 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 108090001008 Avidin Proteins 0.000 description 1
• 101100243548 Caenorhabditis elegans pfd-2 gene Proteins 0.000 description 1
• 101100257262 Caenorhabditis elegans soc-1 gene Proteins 0.000 description 1
• 101100481016 Caenorhabditis elegans tag-325 gene Proteins 0.000 description 1
• 229940127291 Calcium channel antagonist Drugs 0.000 description 1
• 229910052686 Californium Inorganic materials 0.000 description 1
• 241000282836 Camelus dromedarius Species 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 102100028892 Cardiotrophin-1 Human genes 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 108091006146 Channels Proteins 0.000 description 1
• 241000251730 Chondrichthyes Species 0.000 description 1
• 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
• 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
• 108020004705 Codon Proteins 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 102000001189 Cyclic Peptides Human genes 0.000 description 1
• 108010069514 Cyclic Peptides Proteins 0.000 description 1
• 241000701022 Cytomegalovirus Species 0.000 description 1
• IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
• 230000004544 DNA amplification Effects 0.000 description 1
• 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
• XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
• CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
• 108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 description 1
• 102000016607 Diphtheria Toxin Human genes 0.000 description 1
• 108010053187 Diphtheria Toxin Proteins 0.000 description 1
• 101100421450 Drosophila melanogaster Shark gene Proteins 0.000 description 1
• 206010013887 Dysarthria Diseases 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 102400001047 Endostatin Human genes 0.000 description 1
• 108010079505 Endostatins Proteins 0.000 description 1
• 241000402754 Erythranthe moschata Species 0.000 description 1
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
• 241001316028 Euphaedusa tau Species 0.000 description 1
• BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
• 108091007911 GSKs Proteins 0.000 description 1
• 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 229920002527 Glycogen Polymers 0.000 description 1
• 102000004103 Glycogen Synthase Kinases Human genes 0.000 description 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
• 108010051696 Growth Hormone Proteins 0.000 description 1
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
• 108090000031 Hedgehog Proteins Proteins 0.000 description 1
• 102000003693 Hedgehog Proteins Human genes 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101001081590 Homo sapiens DNA-binding protein inhibitor ID-1 Proteins 0.000 description 1
• 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
• 101000874160 Homo sapiens Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial Proteins 0.000 description 1
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
• 102000003839 Human Proteins Human genes 0.000 description 1
• 108090000144 Human Proteins Proteins 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 102000004157 Hydrolases Human genes 0.000 description 1
• 108090000604 Hydrolases Proteins 0.000 description 1
• 102000004877 Insulin Human genes 0.000 description 1
• 108090001061 Insulin Proteins 0.000 description 1
• 108010001127 Insulin Receptor Proteins 0.000 description 1
• 102100036721 Insulin receptor Human genes 0.000 description 1
• 102000006992 Interferon-alpha Human genes 0.000 description 1
• 108010047761 Interferon-alpha Proteins 0.000 description 1
• 102000003996 Interferon-beta Human genes 0.000 description 1
• 108090000467 Interferon-beta Proteins 0.000 description 1
• 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 1
• 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
• 102100020873 Interleukin-2 Human genes 0.000 description 1
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• 108010063738 Interleukins Proteins 0.000 description 1
• 102000015696 Interleukins Human genes 0.000 description 1
• 102000004195 Isomerases Human genes 0.000 description 1
• 108090000769 Isomerases Proteins 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 108010015340 Low Density Lipoprotein Receptor-Related Protein-1 Proteins 0.000 description 1
• 102100040705 Low-density lipoprotein receptor-related protein 8 Human genes 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 239000005089 Luciferase Substances 0.000 description 1
• DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
• 102000004317 Lyases Human genes 0.000 description 1
• 108090000856 Lyases Proteins 0.000 description 1
• PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical group COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
• 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 108050003475 Neuregulin Proteins 0.000 description 1
• 102000014413 Neuregulin Human genes 0.000 description 1
• 108090000556 Neuregulin-1 Proteins 0.000 description 1
• 102400000058 Neuregulin-1 Human genes 0.000 description 1
• 101100109292 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) arg-13 gene Proteins 0.000 description 1
• 102000003683 Neurotrophin-4 Human genes 0.000 description 1
• 102100033857 Neurotrophin-4 Human genes 0.000 description 1
• 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 1
• 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 101100491259 Oryza sativa subsp. japonica AP2-2 gene Proteins 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 239000002033 PVDF binder Substances 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 102100036660 Persephin Human genes 0.000 description 1
• 108010004729 Phycoerythrin Proteins 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 102100021923 Prolow-density lipoprotein receptor-related protein 1 Human genes 0.000 description 1
• 108010039491 Ricin Proteins 0.000 description 1
• 241000220317 Rosa Species 0.000 description 1
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
• 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 102100038803 Somatotropin Human genes 0.000 description 1
• QTENRWWVYAAPBI-YZTFXSNBSA-N Streptomycin sulfate Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@H]1[C@H](N=C(N)N)[C@@H](O)[C@H](N=C(N)N)[C@@H](O)[C@@H]1O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@H]1[C@H](N=C(N)N)[C@@H](O)[C@H](N=C(N)N)[C@@H](O)[C@@H]1O QTENRWWVYAAPBI-YZTFXSNBSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
• 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
• 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
• 108010033576 Transferrin Receptors Proteins 0.000 description 1
• 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
• 108010009583 Transforming Growth Factors Proteins 0.000 description 1
• 102000009618 Transforming Growth Factors Human genes 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• 206010047513 Vision blurred Diseases 0.000 description 1
• 229960004373 acetylcholine Drugs 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 150000003978 alpha-halocarboxylic acids Chemical class 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 230000005875 antibody response Effects 0.000 description 1
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
• 230000000890 antigenic effect Effects 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 238000011190 asparagine deamidation Methods 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 150000001510 aspartic acids Chemical class 0.000 description 1
• FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
• 238000003149 assay kit Methods 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 230000003376 axonal effect Effects 0.000 description 1
• 244000052616 bacterial pathogen Species 0.000 description 1
• 210000004082 barrier epithelial cell Anatomy 0.000 description 1
• 238000013542 behavioral therapy Methods 0.000 description 1
• 102000005936 beta-Galactosidase Human genes 0.000 description 1
• 108010005774 beta-Galactosidase Proteins 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 239000013060 biological fluid Substances 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 229910052797 bismuth Inorganic materials 0.000 description 1
• JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 239000000480 calcium channel blocker Substances 0.000 description 1
• HGLDOAKPQXAFKI-UHFFFAOYSA-N californium atom Chemical compound [Cf] HGLDOAKPQXAFKI-UHFFFAOYSA-N 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
• 108010041776 cardiotrophin 1 Proteins 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 239000013522 chelant Substances 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 239000000544 cholinesterase inhibitor Substances 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 230000003930 cognitive ability Effects 0.000 description 1
• 230000003920 cognitive function Effects 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 230000009827 complement-dependent cellular cytotoxicity Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 239000008139 complexing agent Substances 0.000 description 1
• 238000004590 computer program Methods 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 239000003431 cross linking reagent Substances 0.000 description 1
• 239000002577 cryoprotective agent Substances 0.000 description 1
• 238000002447 crystallographic data Methods 0.000 description 1
• 150000001944 cysteine derivatives Chemical class 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 238000012303 cytoplasmic staining Methods 0.000 description 1
• 230000003436 cytoskeletal effect Effects 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 238000007405 data analysis Methods 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 230000002328 demineralizing effect Effects 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• 235000015872 dietary supplement Nutrition 0.000 description 1
• 238000001085 differential centrifugation Methods 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
• 229960003530 donepezil Drugs 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 238000001493 electron microscopy Methods 0.000 description 1
• 210000002308 embryonic cell Anatomy 0.000 description 1
• 230000002996 emotional effect Effects 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 239000002158 endotoxin Substances 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000004890 epithelial barrier function Effects 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000003203 everyday effect Effects 0.000 description 1
• 231100000776 exotoxin Toxicity 0.000 description 1
• 239000002095 exotoxin Substances 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
• 238000002060 fluorescence correlation spectroscopy Methods 0.000 description 1
• 238000001917 fluorescence detection Methods 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 238000013467 fragmentation Methods 0.000 description 1
• 238000006062 fragmentation reaction Methods 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 230000005021 gait Effects 0.000 description 1
• 229960003980 galantamine Drugs 0.000 description 1
• ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
• 238000002523 gelfiltration Methods 0.000 description 1
• 238000012239 gene modification Methods 0.000 description 1
• 238000001415 gene therapy Methods 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 108010070004 glucose receptor Proteins 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 150000002307 glutamic acids Chemical class 0.000 description 1
• 102000005396 glutamine synthetase Human genes 0.000 description 1
• 108020002326 glutamine synthetase Proteins 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 229940096919 glycogen Drugs 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 239000000122 growth hormone Substances 0.000 description 1
• 230000010005 growth-factor like effect Effects 0.000 description 1
• 125000001475 halogen functional group Chemical group 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
• 102000049143 human ID1 Human genes 0.000 description 1
• 102000045360 human SDHB Human genes 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
• 238000005286 illumination Methods 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 150000003949 imides Chemical class 0.000 description 1
• 230000002163 immunogen Effects 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 230000016784 immunoglobulin production Effects 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 229940125396 insulin Drugs 0.000 description 1
• 230000002608 insulinlike Effects 0.000 description 1
• 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
• 229940047122 interleukins Drugs 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000000185 intracerebroventricular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229910052741 iridium Inorganic materials 0.000 description 1
• GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 210000003292 kidney cell Anatomy 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 231100000863 loss of memory Toxicity 0.000 description 1
• 108010031117 low density lipoprotein receptor-related protein 8 Proteins 0.000 description 1
• HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
• 230000000527 lymphocytic effect Effects 0.000 description 1
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 229940126601 medicinal product Drugs 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
• 229960004640 memantine Drugs 0.000 description 1
• 210000001259 mesencephalon Anatomy 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 239000004005 microsphere Substances 0.000 description 1
• 108091011150 microtubule binding proteins Proteins 0.000 description 1
• 102000021160 microtubule binding proteins Human genes 0.000 description 1
• 239000006151 minimal media Substances 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 239000010413 mother solution Substances 0.000 description 1
• 239000003471 mutagenic agent Substances 0.000 description 1
• 210000000478 neocortex Anatomy 0.000 description 1
• 238000007857 nested PCR Methods 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 210000004179 neuropil Anatomy 0.000 description 1
• 210000002511 neuropil thread Anatomy 0.000 description 1
• 229940097998 neurotrophin 4 Drugs 0.000 description 1
• 239000000346 nonvolatile oil Substances 0.000 description 1
• 238000002515 oligonucleotide synthesis Methods 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 239000001048 orange dye Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 230000010355 oscillation Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 230000005298 paramagnetic effect Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 230000006919 peptide aggregation Effects 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
• 108010070453 persephin Proteins 0.000 description 1
• 238000002823 phage display Methods 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000001766 physiological effect Effects 0.000 description 1
• 229920000747 poly(lactic acid) Polymers 0.000 description 1
• 229920002401 polyacrylamide Polymers 0.000 description 1
• 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
• 229920002859 polyalkenylene Polymers 0.000 description 1
• 239000004633 polyglycolic acid Substances 0.000 description 1
• 239000004626 polylactic acid Substances 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000004321 preservation Methods 0.000 description 1
• 210000001236 prokaryotic cell Anatomy 0.000 description 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 230000004850 protein–protein interaction Effects 0.000 description 1
• 230000005180 public health Effects 0.000 description 1
• 230000001698 pyrogenic effect Effects 0.000 description 1
• 229940043131 pyroglutamate Drugs 0.000 description 1
• 238000003127 radioimmunoassay Methods 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 238000003753 real-time PCR Methods 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 238000007670 refining Methods 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 125000006853 reporter group Chemical group 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 229910052702 rhenium Inorganic materials 0.000 description 1
• HYERJXDYFLQTGF-UHFFFAOYSA-N rhenium Chemical compound [Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re][Re] HYERJXDYFLQTGF-UHFFFAOYSA-N 0.000 description 1
• PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
• 210000003296 saliva Anatomy 0.000 description 1
• 229940016590 sarkosyl Drugs 0.000 description 1
• 108700004121 sarkosyl Proteins 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 230000009919 sequestration Effects 0.000 description 1
• 229940121356 serotonin receptor antagonist Drugs 0.000 description 1
• 208000026473 slurred speech Diseases 0.000 description 1
• KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 239000012064 sodium phosphate buffer Substances 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 238000005063 solubilization Methods 0.000 description 1
• 230000007928 solubilization Effects 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 210000004988 splenocyte Anatomy 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 230000010473 stable expression Effects 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 230000003068 static effect Effects 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 238000000856 sucrose gradient centrifugation Methods 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
• 229960005314 suramin Drugs 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 230000009747 swallowing Effects 0.000 description 1
• 230000005469 synchrotron radiation Effects 0.000 description 1
• 229960001685 tacrine Drugs 0.000 description 1
• YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
• 150000004905 tetrazines Chemical class 0.000 description 1
• 238000001757 thermogravimetry curve Methods 0.000 description 1
• AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 1
• JADVWWSKYZXRGX-UHFFFAOYSA-M thioflavine T Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C1=[N+](C)C2=CC=C(C)C=C2S1 JADVWWSKYZXRGX-UHFFFAOYSA-M 0.000 description 1
• 230000001732 thrombotic effect Effects 0.000 description 1
• 208000008732 thymoma Diseases 0.000 description 1
• 229960000187 tissue plasminogen activator Drugs 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000005026 transcription initiation Effects 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 230000010474 transient expression Effects 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 102000003390 tumor necrosis factor Human genes 0.000 description 1
• WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
• 229910052721 tungsten Inorganic materials 0.000 description 1
• 239000010937 tungsten Substances 0.000 description 1
• ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
• HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 238000002255 vaccination Methods 0.000 description 1
• 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 239000012808 vapor phase Substances 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 210000005253 yeast cell Anatomy 0.000 description 1
• 229940124648 γ-Secretase Modulator Drugs 0.000 description 1